Neurodevelopmental schizophrenia: obstetric complications, birth weight, premorbid social withdrawal and learning disabilities.

Neurodevelopmental schizophrenia seems to be caused by impaired cerebral development and is supposed to be associated with obstetric complications (OCs), poor premorbid adjustment, schizotypal or schizoid personality traits and negative symptoms. In the present study, 36 schizophrenic and schizoaffective patients and their same-sex, healthy siblings were recruited. They were diagnosed according to DSM-III-R, using structured psychiatric interviews and a consensus of 2 psychiatrists. Information on OCs, birth weight, premorbid social and learning functioning was obtained from their mothers. The main results show significant differences in OCs, birth weight, premorbid social and learning functioning between patients and their same-sex, healthy siblings. Using multivariate analyses, both premorbid variables were again identified to discriminate well between affected and unaffected siblings. Our findings seem to confirm the concept of schizophrenia as a neurodevelopmental process.

Linkage of mood disorders with D2, D3 and TH genes: a multicenter study.

BACKGROUND: It has been suggested that the dopaminergic system is involved in the pathophysiology of mood disorders. We conducted a multicenter study of families with mood disorders, to investigate a possible linkage with genes coding for dopamine receptor D2, dopamine receptor D3 and tyrosine hydroxylase (TH). METHODS: Twenty three mood disorder pedigrees collected within the framework of the European Collaborative Project on Affective Disorders were analyzed with parametric and non-parametric linkage methods. Various potential phenotypes were considered, from a narrow (only bipolar as affected) to a broad (bipolar+major depressive+schizoaffective disorders) definition of affection status. RESULTS: Parametric analyses excluded linkage for all the candidate genes, even though small positive LOD (Limit of Detection) scores were observed for TH in three families. Non-parametric analyses yielded negative results for all markers. CONCLUSION: The D2 and D3 dopamine receptors were, therefore, not a major liability factor for mood disorders in our sample, whereas TH may play a role in a subgroup of patients.

Confirmation of association between expanded CAG/CTG repeats and both schizophrenia and bipolar disorder.

Recent studies have suggested that expanded CAG/CTG repeats contribute to the genetic aetiology of schizophrenia and bipolar disorder. However, the nature of this contribution is uncertain and difficult to predict from other known trinucleotide repeat diseases that display much simpler patterns of inheritance. We have sought to replicate and extend earlier findings using Repeat Expansion Detection in an enlarged sample of 152 patients with schizophrenia, 143 patients with bipolar disorder, and 160 controls. We have also examined DNA from the parents of 62 probands with schizophrenia or bipolar disorder. Our results confirm our earlier, preliminary findings of an association between expanded trinucleotide repeats and both schizophrenia and bipolar disorder. However, our data do not support the hypothesis that trinucleotide repeat expansion can alone explain the complex patterns of inheritance of the functional psychoses neither can this mechanism fully explain apparent anticipation.

Schizophrenia and the dopamine-beta-hydroxylase gene: results of a linkage and association study.

Alterations in dopamine neurotransmission and disturbed norepinephrine activity have been implicated in the pathogenesis of schizophrenia. We considered the dopamine-beta-hydroxylase (DBH) gene located on the long arm of chromosome 9 (9q34.3) as a candidate gene for schizophrenia. DBH catalyzes the synthesis of norepinephrine from dopamine in noradrenergic neurons. In addition to DBH we used in the linkage study DNA markers ABL (centromeric) and D9S114 (telomeric). The aim of this study was to test linkage and association between PCR-based genotyped markers and schizophrenia. A simulation was done to investigate the power of our sample. In 34 Austrian families we could not detect linkage between schizophrenia and schizophrenia spectrum disorders and the three genetic markers. We could not find any significant deviation in allelic or genotypic distribution from expectations. Based on our results we conclude that the DBH gene seems to have no strong contribution in the etiology of schizophrenia.

[Huntington chorea: (CAG)n repeats on gene IT 15 in Austria]. / Chorea Huntington: Die (CAG)n-Sequenz am Gen IT 15 in Osterreich.

In March 1993 the gene IT 15 was identified on chromosome 4p and it was demonstrated that it contained an unstable (CAG)n trinucleotide repeat that is elongated in patients with Huntington's chorea (HC). Persons with more than 37 (CAG)n repeats tend to have a higher risk of developing the disease. Testing the (CAG)n repeats in Austrian HC patients with PCR techniques shows correspondence between the clinical diagnosis of HC and genotypes [more than 42 (CAG)n repeats]. There was a weak correlation between the number of (CAG)n repeats and age of onset, however, this finding is without diagnostic value due to the scatter of the values.

The season of birth of schizophrenics and schizoaffectives.

We examined the birth distribution of 2,450 schizophrenic and 682 schizoaffective patients first admitted between 1971 and 1992 to the University Hospital for Psychiatry in Vienna. Our data showed an excess of schizophrenic births in the first quarter of the year and a deficit in the third quarter compared with expectation from census data. The quarterly distribution of schizophrenic births seemed to be different from the one of of schizoaffective patients. In schizoaffectives an excess of births in the first quarter of the year was present, but no other deviation from expectation.

Non-concordance by gender for schizophrenia and related disorders in sibships.

We analysed gender-concordance rates among 29 prospectively sampled schizophrenic probands and their 39 affected and 71 unaffected siblings. We did not find any unusual concordance rates. We found no same-gender concordance particularly in siblings affected by schizophrenia and related disorders. We considered unaffected siblings in an additional attempt to make valid and unbiased comparisons between genders, but this reduced the number of informative sibships to 20. We stratified the siblings of probands by sibship and by the proband's gender in order to check gender distribution within families. The data do not support hypotheses that schizophrenia is pseudo-autosomal or male-female chromosomally transmitted.